Laboratory of Nanobiotechnology, Institute of Biotechnology, Federal University of Uberlândia, Uberlândia 38402-022, MG, Brazil.
Department of Medical Imaging, Hematology and Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirao Preto 14040-900, SP, Brazil.
Int J Mol Sci. 2024 Oct 3;25(19):10641. doi: 10.3390/ijms251910641.
Sepsis poses a significant challenge due its lethality, involving multiple organ dysfunction and impaired immune responses. Among several factors affecting sepsis, monocytes play a crucial role; however, their phenotype, proteomic profile, and function in septic shock remain unclear. Our aim was to fully characterize the subpopulations and proteomic profiles of monocytes seen in septic shock cases and discuss their possible impact on the disease. Peripheral blood monocyte subpopulations were phenotype based on CD14/CD16 expression by flow cytometry, and proteins were extracted from the monocytes of individuals with septic shock and healthy controls to identify changes in the global protein expression in these cells. Analysis using 2D-nanoUPLC-UDMSE identified 67 differentially expressed proteins in shock patients compared to controls, in which 44 were upregulated and 23 downregulated. These proteins are involved in monocyte reprogramming, immune dysfunction, severe hypotension, hypo-responsiveness to vasoconstrictors, vasodilation, endothelial dysfunction, vascular injury, and blood clotting, elucidating the disease severity and therapeutic challenges of septic shock. This study identified critical biological targets in monocytes that could serve as potential biomarkers for the diagnosis, prognosis, and treatment of septic shock, providing new insights into the pathophysiology of the disease.
脓毒症因其致命性、涉及多个器官功能障碍和免疫反应受损而构成重大挑战。在影响脓毒症的几个因素中,单核细胞起着关键作用;然而,其在感染性休克中的表型、蛋白质组学特征和功能仍不清楚。我们的目的是全面描述感染性休克患者单核细胞的亚群和蛋白质组学特征,并讨论它们对疾病可能产生的影响。通过流式细胞术根据 CD14/CD16 的表达对外周血单核细胞亚群进行表型分析,并从感染性休克患者和健康对照者的单核细胞中提取蛋白质,以鉴定这些细胞中整体蛋白质表达的变化。使用 2D-nanoUPLC-UDMSE 分析,与对照组相比,休克患者中有 67 种蛋白质表达存在差异,其中 44 种上调,23 种下调。这些蛋白质涉及单核细胞重编程、免疫功能障碍、严重低血压、对血管收缩剂反应性降低、血管舒张、内皮功能障碍、血管损伤和凝血,阐明了感染性休克的疾病严重程度和治疗挑战。本研究确定了单核细胞中的关键生物学靶标,它们可能成为感染性休克诊断、预后和治疗的潜在生物标志物,为该疾病的病理生理学提供了新的见解。